Botulinum neurotoxin A subtype 2 reduces pathological behaviors more effectively than subtype 1 in a rat Parkinson's disease model

Biochem Biophys Res Commun. 2014 May 2;447(2):311-4. doi: 10.1016/j.bbrc.2014.03.146. Epub 2014 Apr 5.

Abstract

Recent reports indicate that interruption of acetylcholine release by intrastriatal injection of botulinum neurotoxin type A (BoNT/A) in a rat Parkinson's disease model reduces pathogenic behavior without adverse side effects such as memory dysfunction. Current knowledge suggests that BoNT/A subtype 1 (BoNT/A1) and BoNT/A subtype 2 (BoNT/A2) exert different effects. In the present study, we compared the effects of BoNT/A1 and BoNT/A2 on rotation behavior and in vivo cleavage of presynaptic protein SNAP-25 in a rat unilateral 6-hydroxydopamine-induced Parkinson's disease model. BoNT/A2 more effectively reduced pathogenic behavior by efficiently cleaving SNAP-25 in the striatum compared with that of BoNT/A1. Our results suggest that BoNT/A2 has greater clinical therapeutic value for treating subjects with Parkinson's disease compared to that of BoNT/A1.

Keywords: Acetylcholine; Botulinum neurotoxin; Parkinson’s disease; Rats; Subtype.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Botulinum Toxins, Type A / administration & dosage*
  • Botulinum Toxins, Type A / adverse effects
  • Choline O-Acetyltransferase / metabolism
  • Corpus Striatum / drug effects
  • Corpus Striatum / metabolism
  • Disease Models, Animal
  • Female
  • Male
  • Oxidopamine / pharmacology
  • Parkinson Disease, Secondary / chemically induced
  • Parkinson Disease, Secondary / drug therapy*
  • Parkinson Disease, Secondary / physiopathology
  • Proteolysis
  • Rats
  • Rotation
  • Synaptosomal-Associated Protein 25 / metabolism

Substances

  • Synaptosomal-Associated Protein 25
  • Oxidopamine
  • Choline O-Acetyltransferase
  • Botulinum Toxins, Type A